There are five major families of cyclic nucleotide phosphodiesterases (PDEs) with distinctive physicochemical/structural and kinetic properties. One class, the so-called cGMP-inhibited low Km cAMP PDE (cGI PDE) is characterized by its high affinity for cAMP and cGMP and specific inhibition of cAMP hydrolysis by cGMP and by certain positive inotropic and vasodilatory drugs (amrinone, milrinone, cilostamide). The cGI PDEs are important in the regulation of myocardial contractility, vascular tonus, platelet aggregation and antilipolytic action of insulin. Little is known concerning the relationships and structural/functional similarities between cGI PDEs from these various tissues. Using partial information from platelet cGI PDE protein, oligonucleotides were synthesized and used for PCR amplification of human heart cDNA library and for screening a rat adipose tissue cDNA library. Two positive cDNA clones (FAT 1 and FAT 2) were isolated and sequenced (Taira, M. et. al., (1992) submitted). Northern analysis showed different tissue distribution for the two. FAT 2 cDNA hybridized with rat heart more than rat adipose tissue RNA, and not with adipocyte cell RNA. Using FAT 2 cDNA as a probe, we screened a rat adipose tissue cDNA library. One of several positive clones (2-12-1; 7.1 kb) was isolated and sequenced. Its nucleotide sequence was more than 90% identical to that human heart cGI PDE, especially in the conserved domain and phosphorylation sites. This clone most likely represents the rat analog of human heart cGI PDE. Whether these cGI PDEs are specific for cardiac or cardiovascular tissues is not certain, since PCR amplification of human aortic cDNA and human liver cDNA with non-degenerate primers revealed the presence of partial human cardiac cGI PDE sequence. Diversity within the cGI PDE gene family is being currently evaluated by PCR amplification of liver and aortic cDNA with degenerate primers.